Utilization of ESWT to restore peripheral vibro-sensory perception in an insensate Type 1 diabetic foot:

An Original Exploratory Case Study.Kenneth Craig,1 Wayne Hing,2 Gwyn Lewis,3 Daniel Poratt,3 Marjorie Walker 4

1Director – Kompass Centre for Shockwave Therapy and Research, Auckland. 2Professor – Research Dept. Bond University, Australia & Assoc. Prof. Health & Rehabilitation Institute, Auckland University of Technology, Auckland. 2Sr. Lecturer Health & Rehabilitation Institute, Auckland University of Technology, Auckland. 3Sr. Lecturer Podiatry Dept. Auckland University of

Technology, Auckland. 4Physiotherapy Student Intern, Auckland University of Technology, Auckland.

Introduction

Peripheral insensitivity due to diabetes polyneuropathy is a common syndrome associated with both types of diabetes that places patients at a greater risk of developing ulcers and the associated complications.

Aim

To introduce ESWT as a potential treatment option and undertake collaborative efforts to further investigate its efficacy in this area.

Table 1. Pre treatment case history, clinical presentation and basic instrumentation and quantitative test yields.

Materials and Method

Case-study involving a 59yr old male patient with a 50yr history of Type 1 diabetes with distal symmetrical sensorimotor polyneuropathy (Table 1).

One limb selected as the treatment limb (Txl), and the other as control (Ctrl). 10g monofilament, 128Hz tuning fork, neurotips, biothesiometer and

electro-sensory stimulation (ESS) measured baseline and post-intervention outcomes. Six sessions of extracorporeal shockwave therapy (ESWT)

was administered over the 1st and 5th metatarsals, lateral and medial malleolus, and the hallux. 500 impulses at 0.10mj/mm² were administered

over each region at 1 week intervals. Co-investigators were blinded to selection of the Txl vs. Ctrl throughout the treatment and follow-up period.

Result

At 8 weeks post-ESWT Txl demonstrated improvements of sensory perception to basic instrumentation such as monofilament (Table 2), neurotips (Table 3) and tuning fork (Table 4), while Ctrl remained unchanged. Txl

required less stimulus utilizing biothesiometer (Baseline average 37.74volts; Post-ESWT avg. 28.04volts) (Table 5) (Figure 2). Similarly detection (DE), discomfort (DC) and pain (PN) thresholds of Txl utilizing ESS required

less stimulus in each domain (Baseline DE: 25mA; 15mA post-ESWT); (Baseline DC: 45mA; 35mA post-ESWT), and (Baseline PN: 135mA; 105mA post-ESWT) (Table 6) (Figure 3). The Ctrl limb demonstrated further

progressive detorioration requiring increased biothesiometer stimulus (Baseline 37.44volts; 40.07volts post trial) (Table 5) (Figure 2) and ESS respectively (Baseline DC: 35mA; 45mA post trial) (Baseline PN: 65m; 75mA post

trial) (Table 6) (Figure 3).

Discussion

Distal sensorimotor polyneuropathy (DPN) is the most common form of neuropathic manifestation in both types of diabetes, and yet despite its prevalence there are currently no effective treatments available to arrest or

modify disease progression other then optimal glyceamic control and education, and these measures will not guarantee that patients will not develop DPN as factors other than hyperglycemia are involved with the

development of this syndrome.1,3 Although the exact mechanism of ESWT is yet to be fully elucidated, a dose dependant stimulus from shockwaves are seen to trigger a neuro-bio-chemical regulatory cascade that result in

the resolution of various osseous, musculoskeletal, vascular and neurologiocal pathology.5,6,8,9,10 Among the physiological impact of shockwaves on human tissue are: increased cell-membrane permeability, stimulus and

regulation of both neural and endothelial nitric oxide synthase (nNOS & eNOS), collagen synthesis, progenitor cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and a host of inflammatory and pain

modulating properties.5,6,8,9,10 Although a variety of components may be responsible for the changes seen in this case-study, VEGF is a component that is of worthwhile mention in this instance as both dated and emerging

evidence indicate that VEGF enhances and supports the growth and regeneration of nerve fibers possibly through a combination of angiogenic, neurotrophic and neuroprotective properties.2,4,7

A pertinent observation noted in this case-study was that, the continued and insidious nature of the neuropathic disease progression was beyond the detection threshold capability of basic clinical instrumentation and was noted when

using quantitative measurements such as biothesiometer and ESS.

Conclusion:

Although case studies are considered anecdotal evidence, the findings of this case-study suggests that ESWT may offer a non-invasive and systemically safe treatment option that induces and regulates the very physiological

components necessary for the reversal of DPN. Further exploration is warranted to further explore the potential use of ESWT for the reversal of vibro-sensory deficits due to DPN in diabetics. This is the first instance where

ESWT has been used in an attempt to restore vibro-sensory insensitivity due to DPN in a diabetic foot.

Reference

1. Boulton A. Medical Treatment of Symptomatic Diabetic Neuropathy. Immunology, Endocrinology & Metabolic Agents in Medicinal Chemistry. 2007; 7, 79 – 86.

2. Carmeliet P & Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature. 2005; 436(7048): 193 – 200.

3. Gale, E. A. M. Glucose control in the UKPDS: what did we learn? Diabetic Medicine. 2008; 25(S2) 9 -12.

4. Lopes PFR, Lisboa BCG, Frattini F, Almeida FM, et. al, Enhamcement of sciatic nerve regenaration after vascular endothelial growth factor (VEGF) gene therapy. Neuropathology and Appliced Neurobiology. 2011; 37: 600 – 612.

5. Mittermayr R, Hartinger J, Antonic V, et al. Extracorporeal Shock Wave Therapy (ESWT) Minimizes Ischemic Tissue Necrosis Irrespective of Application Time and Promotes Tissue Revascularization by Stimulating Angiogenesis. Ann Surg 2011;253:1024–1032.

6. Nortanicola A, Morreti L, Tafuri S el al. Shockwave therapy in the management of Complex Regional Pain Syndrome of the femoral condyle of the knee. Ultrasound Med Biol. 2010; 36(6):874-9.

7. Rosenstein JM & Krum JM. New roles for VEGF in nervous tissue – beyond blood vessels. 2004;187: 246 – 253.

8. Saginni R, Figus A, Troccola A et al. EXTRACORPOREAL SHOCK WAVE THERAPY FOR MANAGEMENT OF CHRONIC ULCERS IN THE LOWER EXTREMITIES. Ultrasound in Med. & Biol. 2008; 34( 8):1261–1271.

9. Vasyuk Y, Hadgegova A, Shkolnik E, et al. Initial Clinical Experience With Extracorporeal Shock Wave Therapy in Treatment of Ischemic Heart Failure. Congestive Heart Failure. 2010;16(5) 226 – 230.

10. Wang C-J, Kuo Y-R, Wu R-W, et al. Extracorporeal Shockwave Treatment for Chronic Diabetic Foot Ulcers. Journal of Surgical Research. 2008 May;152 (1)

Case Clinical Presentation Left Limb – Baseline Right Limb – Baseline

Male – 59yrs.

Health Professional

• 50yr Hx T1DM

• Insulin glargine

26units

• Insulin lispro

4/10 units

• Symmetrical sensory deficits (see next 2 columns)

• Pedal pulses – Present bilaterally

• Deep tendon reflexes – Absent bilaterally

• Paresthesia (burning sensations) – bilaterally

• Dyesthesia – Left Hallux & 5th digit

• Mild muscle weakness – bilateral leg compartments

• Gait and balance – Unremarkable

• Skin temperature to touch – Unremarkable

• Skin condition – Unremarkable

• Gait and balance - Unremarkable

• Neurotip – Not distinguished .

• 10g monofilament - 4/10 dermatomes

• 128Hz tuning fork – Undetected

• Light touch – Undetected

• Hot / Cold – Detected

• Skin surface temperature – 27.0˚C

• Biothesiometer average – 37.74 volts

Electro-stimulation average:

• Detection (DE) – 25mA

• Discomfort (DC) – 45mA

• Pain (PN) – 135mA

• Neurotip – Not distinguished .

• 10g monofilament - 4/10 dermatomes

• 128Hz tuning fork – Undetected

• Light touch – Undetected

• Hot / Cold – Detected

• Skin surface temperature – 27.5˚C

• Biothesiometer average – 37.44 volts

Electro Sensory Stimulation (ESS) average:

• Detection (DE) – 30mA

• Discomfort (DC) – 35mA

• Pain (PN) – 65mA

Figure 1. A shockwave (soundwave)

propagated by a controlled underwater explosion

using an electro-hydraulic generator. The

soundwave is focused onto the region of interest

using ultrasound gel as the transmission medium

for the wave to penetrate tissue.

Device utilized in this study was an electro-

hydraulic OrthoSpec OR2 operated by KC in the

presence of an intern observer (MW) to ensure

treatments were carried out devoid of patient

coaching.

Region Baseline

Txl.

Post ESWT

Txl.

Baseline

Ctrl.

Post Study

Ctrl,

Hallux XX ++ XX XX

1st MTPJ XX ++ XX XX

3th MTPJ XX ++ XX XX

5th MTPJ XX ++ XX XX

Calcaneus XX XX XX XX

Region Baseline

Txl.

Post ESWT

Txl.

Baseline

Ctrl.

Post Study

Ctrl.

Hallux XX ++ XX XX

3rd Phalangeal pulp XX ++ XX XX

5th Phalangeal pulp ++ ++ ++ ++

1st MTPJ XX ++ XX XX

3rd MTPJ XX ++ XX XX

5th MTPJ XX ++ XX XX

Medial mid-arch ++ ++ ++ ++

Lateral mid-arch ++ ++ ++ ++

Doral foot region ++ ++ ++ ++

Region Baseline

Average Txl.

Post-ESWT

Average Txl.

Change Value

Txl.

Baseline

Average Ctrl.

Post-study

Average Ctrl.

Change value

Ctrl.

Hallux 44.6 27.3 -17.3 44.6 45.0 +0.4

1st MTPJ 39.6 26.0 -13.6 32.0 38.6 +12.6

5th MTPJ 32.6 25.0 -7.6 28.0 31.6 +3.6

Lateral Malleolus 36.6 28.3 - 8.3 42.0 43.3 +1.3

Medial Malleolus 35.3 33.6 -1.7 40.6 41.6 +1.0

Table 4. Sensitivity to 128Hz tuning fork at 8 weeks. XX (Not Detected), ++ (Detected)

Table 5. Comparison of the average biothesiometer stimulus detection between Txl vs Ctrl at 8 weeks. Three (3) readings were taken over each

region with a 5 minute interval in between. Baseline, Post-ESWT & Post study figures are the average of the 3 readings. Biothesiometer

assessment was conducted by a blinded investigator (DP) with KC & MW as observers.

Table 2. Sensitivity to 10g monofilament at 8 weeks post-intervention. XX (Not detected), ++ (Detected).

Table 3. Sensitivity to Neurotips (sharp vs blunt) stimulus at 8weeks. XX (Not detected), ++ (Detected).

Region BaselineTxl.

Post ESWT\Txl BaselineCtrl.

Post StudyCtrl.

Hallux XX ++ XX XX

1st MTPJ XX ++ XX XX

5th MTPJ XX ++ XX XX

Lateral Malleolus XX ++ XX XX

Medial Malleolus XX ++ XX XX

Domain BaselineTxl

Post ESWTTxl

BaselineCtrl.

Post StudyCtrl.

Detection (DE) 25 15 (-10) 30 20 (-10)

Disconfort (DC) 45 35 (-10) 35 45 (+10)

Pain (PN) 135 105 (-30) 65 75 (+10)Table 6. Comparison of the average electro sensory stimulation (ESS) testing the domain of: stimulus detection, stimulus induced discomfort and

stimulus induced pain. Material used was a Digimeter (model DS7A), used to send an electrical impulses graduated at 5miliamperes (mA ‘s) to

determine sensory nerve conduction. The nerve being tested in this instance was the tibial nerve, as it innervates the regions being treated (with

the exception of the lateral malleolus). Location of electrodes were attached just inferior to the medial malleolus of each foot. Three (3) readings

were taken from each foot at 15 minute intervals. Confounding observation was that Ctrl required less stimulus in the domain of detection, while

all other tests on Ctrl demonstrated continued deterioration. ESS was conducted by a blinded investigator (GL) with KC & MW as observers.

Figure 2. Graphical depiction of

sensory changes at 8 weeks to

stimulus to a biothesiometer.

Green bars (Txl).

Red bars (Ctrl).

Figure 3. Graphical description of

sensory changes at 8 weeks to ESS.

Green bars (Txl)

Red (Ctrl)